Sucralfate is used as a therapeutic agent in the treatment of gastritis, and gastric and duodenal ulcers.
The selective adhesion of sucralfate on the ulcer or area of inflammation is crucial for the manifestation of sucralfate's therapeutic effects. Sucralfate's physiological features are as follows: sucralfate's particles are non-selectively adhered on the tissue protein; sucralfate-adheres to the injured area upon contact with the gastric juice, which increases the viscosity of the sucralfate; and through the manifestation of a combined action which binds the sucralfate to the pepsin dispersed in the stomach and consequently inactivates the pepsin, the sucralfate improves the organism's recovery mechanism and promotes the functioning of the organism's defense system resulting in cure of the ulcer or inflammation.
As described in Japanese Patent Publication Nos. 44-11673 and 44-16037, sucralfate is obtained by reaction between the salts of sucrose sulfate and basic aluminum chloride, and the resulting wet powder is dispersed, and then heat drying (spray drying). The resulting dry powder is used as the bulk material when producing solid preparations due to ease of production.
Taking into account sucralfate's insolubility in water and its mechanism of adhesion on protein, it is important to mill the sucralfate as finely as possible in order to increase its surface area.
Conventionally, the sucralfate aqueous suspension has been prepared by mechanically milling sucralfate dry powder, obtained from wet powder by heat-drying, and then recombining the dry powder with water and then preparing the final product. This method of production is not considered technologically advanced due to certain inherent flaws; specifically, (1) this method of production, which consists of a process of drying, milling, and then resuspending the dry powder in water, is operationally defective and entails high costs, (2) there is considerable variation in particle size due to milling of the powder in a dried form, (3) there are pollution problems which arise in the workplace due to fine powder escaping during milling, and (4) pollution is likely to occur due to escaping particles of milled sucralfate powder when filling and sealing containers or when adjusting the production process.
Moreover, since the conventional method requires that once reaction with basic aluminum chloride is complete the resulting sucralfate wet powder be separated by centrifugal manipulation and then dried, it was not possible to design an industrially successive or continuous production process or to plan for efficiency in mass production.